Tick-borne encephalitis is caused by tick-borne encephalitis virus (TBEV; Flaviviridae, genus Flavivirus) which is distributed in an endemic pattern over a wide territory of Europe and northern Asia within the range of the main ixodid tick vectors, Ixodes ricinus (European subtype) and I. persulcatus (Siberian and far eastern subtypes). TBEV, as an arbovirus, relies on two different types of hosts for its transmission cycles: ticks which act as both virus vectors and long-term reservoir hosts, and vertebrates that amplify the virus infection by acting as a source of virus for feeding ticks. Reciprocal specific interactions between TBEV and tick vector, TBEV and vertebrate host, and, between tick vector and vertebrate host in the appropriate environment of the specific geographical area create in a concerted manner unique conditions for virus to perpetuate its transmission cycles and survive.

TBEV survival is based on the intimate ecological association with I. ricinus, or alternatively, I. persulcatus ticks having three developmental stages (larvae, nymphs and adults) overlaping in their activity and feeding strategy with a preference for certain selected vertebrate hosts. The role of vertebrate species as amplifying hosts is highly specific with only a few species efficiently supporting TBEV transmission. Among tested species Apodemus flavicollis field mice were the most efficient amplifying hosts of TBEV. Coincident aggregated distribution of I. ricinus larvae and nymphs was highest on A. flavicollis as observed in western Slovakia. This specific feature consistently increased the number of infectible larvae feeding alongside potentially infected nymphs and was characteristic for tested natural foci of infection.

Human infections occur via an infected tick bite, or, alternatively and less frequently, via drinking of row goat or sheep milk. Exposed groups such as forest workers are in TBEV endemic areas at high risk of infection and should be preferentially vaccinated.